ω-Aryl-PGD compounds

ABSTRACT

Prostaglandin analogs with the following cyclopentane ring structure: ##STR1## are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for some of the same pharmacological purposes as the prostaglandins, particularly and especially as blood platelet aggregation inhibitors.

The present application is a divisional application of Ser. No. 614,244, filed Sept. 17, 1975, now pending. Likewise, U.S. Ser. No. 809,248, filed June 23, 1977 is a divisional application of Ser. No. 614,244.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from Ser. No. 809,248, now U.S. Pat. No. 4,099,014. 

I claim:
 1. A prostaglandin analog of the formula ##STR2## WHEREIN D is ##STR3## wherein Y is cis--CH═CH--, trans--CH═CH--, or --CH₂ CH₂ --;wherein Z₄ is(1) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (3) cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --CF₂ --, or (5) --(CH₂)₃ --(CH₂)_(g) --CH₂ --, wherein g is one, 2, or 3; Wherein M₁ is ##STR4## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₁ is ##STR5## or a mixture of ##STR6## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is hydrogen or fluoro only when the other is hydrogen or fluoro; Wherein Z₃ is oxa or methylene; wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that Z₃ is oxa only when R₃ and R₄ are hydrogen or methyl, being the same or different; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation; with the further proviso that D is ##STR7## only when Y is --CH₂ CH₂ --.
 2. A compound according to claim 1, wherein M₁ is ##STR8##
 3. A compound according to claim 1, wherein M₁ is ##STR9##
 4. A compound according to claim 3, wherein D is ##STR10## and Y is --CH₂ CH₂ --.
 5. A compound according to claim 4, wherein Z₃ is methylene.
 6. A compound according to claim 5, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 7. A compound according to claim 6, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 8. A compound according to claim 7, wherein g is one.
 9. A compound according to claim 8, wherein R₅ and R₆ are both hydrogen.
 10. A compound according to claim 9, wherein R₃ and R₄ are both hydrogen.
 11. 2,2-Difluoro-17-phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD.sub.2, a compound according to claim
 10. 12. A compound according to claim 6, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 13. A compound according to claim 12, wherein g is
 3. 14. A compound according to claim 13, wherein R₅ and R₆ are both hydrogen.
 15. A compound according to claim 14, wherein R₃ and R₄ are both hydrogen.
 16. 2a,2b-Dihomo-17-phenyl-18,19,20-trinor-13, 14-dihydro-9,10-didehydro-9-deoxy-PGD₁ ; a compound according to claim
 15. 17. A compound according to claim 12, wherein g is one.
 18. A compound according to claim 17, wherein R₅ and R₆ are both hydrogen.
 19. A compound according to claim 18, wherein R₃ and R₄ are both hydrogen.
 20. 17-Phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₂, a compound according to claim
 19. 21. A compound according to claim 6, wherein Z₄ is cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 22. A compound according to claim 21, wherein g is one.
 23. A compound according to claim 22, wherein R₅ and R₆ are both hydrogen.
 24. A compound according to claim 23, wherein R₃ and R₄ are both hydrogen.
 25. cis-4,5-Didehydro-17-phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁, a compound according to claim
 24. 26. A compound according to claim 6, wherein Z₄ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --.
 27. A compound according to claim 26, wherein g is one.
 28. A compound according to claim 27, wherein R₅ and R₆ are both hydrogen.
 29. A compound according to claim 28, wherein R₃ and R₄ are both hydrogen.
 30. 2,2-Difluoro-17-phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD.sub.1, a compound according to claim
 29. 31. A compound according to claim 6, wherein Z₄ is --(CH₂)₃ --(CH₂)_(g) --CH₂ --.
 32. A compound according to claim 31, wherein g is
 3. 33. A compound according to claim 32, wherein R₅ and R₆ are both hydrogen.
 34. A compound according to claim 33, wherein R₃ and R₄ are both hydrogen.
 35. 2a,2b-Dihomo-17-phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD.sub.1, a compound according to claim
 34. 36. A compound according to claim 31, wherein g is one.
 37. A compound according to claim 36, wherein R₅ and R₆ are both hydrogen.
 38. A compound according to claim 37, wherein R₃ and R₄ are both hydrogen.
 39. 17-Phenyl-18,19,20-trinor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁, a compound according to claim
 38. 40. A compound according to claim 4, wherein Z₃ is oxa.
 41. A compound according to claim 40, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 42. A compound according to claim 41, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 43. A compound according to claim 42, wherein R₅ and R₆ are both hydrogen.
 44. A compound according to claim 43, wherein R₃ and R₄ are both hydrogen.
 45. 2,2-Difluoro-16-phenoxy-17,18,19,20-tetranor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₂, a compound according to claim
 44. 46. A compound according to claim 41, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 47. A compound according to claim 46, wherein g is
 3. 48. A compound according to claim 47, wherein R₅ and R₆ are both hydrogen.
 49. A compound according to claim 48, wherein R₃ and R₄ are both hydrogen.
 50. 2a,2b-Dihomo-16-phenoxy-17,18,19,20-tetranor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₂, a compound according to claim
 49. 51. A compound according to claim 46, wherein g is one.
 52. A compound according to claim 51, wherein R₅ and R₆ are both hydrogen.
 53. A compound according to claim 52, wherein R₃ and R₄ are both hydrogen.
 54. 16-Phenoxy-17,18,19,20-tetranor-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₂, a compound according to claim
 53. 55. A compound according to claim 41, wherein Z₄ is cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 56. A compound according to claim 55, wherein g is one.
 57. A compound according to claim 56, wherein R₅ and R₆ are both hydrogen.
 58. A compound according to claim 57, wherein R₃ and R₄ are both hydrogen.
 59. A compound according to claim 3, wherein D is ##STR11##
 60. A compound according to claim 59, wherein Z₃ is methylene.
 61. A compound according to claim 60, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 62. A compound according to claim 61, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, or cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 63. A compound according to claim 62, wherein g is one.
 64. A compound according to claim 63, wherein R₅ and R₆ are both hydrogen.
 65. A compound according to claim 64, wherein R₃ and R₄ are both hydrogen.
 66. 2,2-Difluoro-17-phenyl-18,19,20-trinor-9-deoxy-PGD₂, a compound according to claim
 65. 67. 17-Phenyl-18,19,20-trinor-9-deoxy-PGD₂, a compound according to claim
 65. 68. cis-4,5-Didehydro-17-phenyl-18,19,20-trinor-9-deoxy-PGD₁, a compound according to claim
 65. 69. A compound according to claim 59, wherein Z₃ is oxa.
 70. A compound according to claim 69, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 71. A compound according to claim 70, wherein Z₄ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, or cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 72. A compound according to claim 71, wherein g is one.
 73. A compound according to claim 72, wherein R₅ and R₆ are both hydrogen.
 74. A compound according to claim 73, wherein R₃ and R₄ are both hydrogen.
 75. 2,2-Difluoro-16-phenoxy-17,18,19,20-tetranor-9-deoxy-PGD₂, a compound according to claim
 74. 76. 16-Phenoxy-17,18,19,20-tetranor-9-deoxy-PGD₂, a compound according to claim
 74. 77. cis-4,5-Didehydro-16-phenoxy-17,18,19,20-tetranor-9-deoxy-PGD₁, a compound according to claim
 74. 